Interview with Pierre J. Magistretti, M.D., Ph.D.

Interview with Pierre J. Magistretti, M.D., Ph.D.

May 3, 2010

Pierre J. Magistretti, M.D., Ph.D. is a vice-chairman of the European Dana Alliance for the Brain (EDAB) and one of its founding members. He is director of the Brain Mind Institute at Ecole Polytechnique Fédérale in Lausanne, Switzerland, and director of the Center for Psychiatric Neuroscience of the Centre Hospitalier Universitaire Vaudois and University of Lausanne. He leads a consortium of several scientists and clinicians from Lausanne, Geneva, and Basel, which has recently been awarded a National Center for Competence in Research grant for collaborative studies on the synaptic bases of mental diseases. The award is for 17.5 million Swiss francs, for an initial period of four years, renewable twice. The grant is part of a program of the Federal Department of Interior to support centers of excellence which are meant to trigger fundamental progress in various fields of knowledge. It is noteworthy that a center on the neurobiology of mental diseases was recognized to be of national importance.

Q: The grant you just received places great importance on a translational program. It brings together basic researchers and clinicians across several fields of research. Can you briefly explain how this interdisciplinary approach will work and how ultimately the integration of bench sciences and clinical applications are significant from a therapeutic point of view?

Magistretti: It is indeed the main challenge of this program. We have addressed it by adopting a combined top-down (bedside-to-bench) and bottom-up (bench-to-bedside) approach that meets around three methodological platforms: imaging, molecular genetics, and behavior. These platforms will allow us to identify what “endophenotypes” are potentially shared by animals and humans. An endophenotype can be viewed as a revealed biomarker, for example, by a brain imaging pattern, by a particular behavioral trait, or by the presence of a unique chemical in the blood, which ideally is connected with a genetic marker. Once this connection is made (through these platforms), studies at the cellular and molecular levels can be conducted in animals, with a degree of invasiveness that is not possible in humans. In the other direction, if certain circuits appear to be involved in a given behavior in animals, they can be instructive for further analysis in humans.

This grant is focused on looking at the synaptic bases of mental disease and has, as one objective, understanding how disease-associated genes alter synaptic function and affect neuronal networks. Could you explain the critical nature of understanding how disease-associated genes can foster our understanding of mental diseases?

Structural brain alterations have been very rarely found to be a defining feature of a given psychiatric disorder. The abnormalities are in the functional dimension. A functional unit of the nervous system for which considerable advances have been made over the last two decades is the synapse. We now have the knowledge and the tools that can guide us in relating molecular and genetic abnormalities at the synapse with mental diseases.

One of the novel approaches of the grant is to bring forward a new generation of psychiatrists with competencies in neuroscience. How will this alter current training and practices? How will this advance patient therapy?

Indeed it would seem pretty obvious that achieving a strong neuroscience background be part of the standard training of a psychiatrist. One would expect a cardiologist to be an expert in cardiac physiology. However, this is far from being the case, at least in Europe, for psychiatry. Most of the “biological” knowledge is restricted to psychopharmacology. Dual training in neuroscience and psychiatry will result in a new generation of psychiatrists who will be able to leverage neuroscientific advances for clinical research studies, potentially opening the way to new therapies. We should not forget that the current therapeutic armamentarium (resources, methods, etc.) available for psychiatry is the result of serendipitous observations made in the late fifties and sixties.

You have a strong commitment to public education and give considerable time to these efforts. How can we encourage the upcoming generation of scientists to see public education as part of their career?

This is a general issue for the public understanding of neuroscience. It is essential that the efforts and time commitment that young scientists put into public education activities, be recognized as part of their career achievements, like teaching for example. This is beginning to be the case, but much remains to be done. As far as the field of psychiatric neuroscience is concerned, an important contribution that public education can do, is to destigmatize psychiatric diseases.